This invention relates to delivery devices and packaging for medicaments, in particular to delivery devices and packaging for the administration of medicaments by inhalation.
The administration of powdered medicaments by inhalation is well-established. One form of delivery device which is employed for this purpose is the pressurised aerosol or metered dose inhaler (MDI). MDI""s are, however, not suitable for use by all patients, eg small children, or for the administration of all medicaments. Also, there is concern about environmental damage caused by the propellants employed in MDI""s. A widely-used alternative is the so-called dry powder inhaler in which medicament powder is dispensed from an elongate gelatine capsule, by causing the capsule to rotate and/or vibrate, into an airstream which is inhaled by the patient. The capsules are pierced. usually at each end. The piercing is carried out in the device by a suitable puncturing mechanism, and it has also been proposed for the capsules to be supplied in pre-pierced form, in packaging which prevents loss of powder from the capsule and the ingress of moisture.
Gelatine capsules, and known drug delivery devices for inhalation, suffer from numerous disadvantages. Disadvantages of MDI""s have been referred to above. So far as dry powder inhalers are concerned, the gelatine capsules are not impervious to moisture. Exposure to the atmosphere can therefore result in absorption of moisture, which in turn may lead to agglomeration of the medicament powder particles. These problems may be particularly acute where as is often the case, the medicament is hygroscopic. As a result, capsules must be packaged in secondary packaging such as a blister package.
Another disadvantage is that the gelatine may be brittle, with the result that the piercing operation may produce shards or fragments which may be inhaled by the patient. This is clearly undesirable. Also, gelatine is a material of biological origin and therefore always contains a certain amount of microbiological organisms, which again is undesirable from the point of view of possible contamination of the medicament.
Removal of the capsule from the secondary packaging and loading it into the device may require a degree of dexterity greater than that possessed by some patients. In addition, the motion of the elongate gelatine capsule within the device may be irregular, leading to incomplete or variable dispensing of the powdered medicament.
Novel drug delivery devices for the administration of medicament by inhalation, and novel forms of packaging for such medicaments, have now been devised, which overcome or substantially mitigate the above-mentioned problems.
According to a first aspect of the invention there is provided a system for the administration of a powdered medicament by inhalation, the system comprising a container containing a unit dose of medicament in powder form, the container having at least one dispensing aperture, and a device having a chamber adapted to receive said container, the device further comprising air inlet means by which air may be drawn into the chamber and mouthpiece means by which air and entrained medicament may be drawn out of the chamber, wherein the chamber is substantially circular or annular in form and, in use, the container follows an orbital path within the chamber.
The system according to the invention is advantageous primarily in that it may provide improved performance in terms of the dispersion of the medicament dispensed from it, ie the proportion of the medicament which is in the form of particles fine enough to penetrate deep into the patient""s airways. Loading of the medicament container into the device is easy to perform. Emptying of the medicament container may be better than with other, known devices, leading to accurate and reproducible dosing. The airflow required to generate motion of the container within the device may be relatively low, enabling the device to be used with confidence by patients with weak lung function. In addition, the device is of compact and simple construction, leading to reduced manufacturing cost and longer lifetime. It may also be possible for a wide range of differently sized medicament containers to be utilised in association with the same device.
The air inlet means are preferably arranged such that air enters the chamber substantially tangentially so as to as to facilitate the orbital motion of the container within the chamber. There are preferably provided a plurality of air inlets, most preferably opening into the chamber at substantially equiangularly spaced positions. The air inlets may include narrowed portions to act as venturi and thereby increase the speed of the airflow.
It is particularly preferred that a part of the wall of the chamber into which the air inlets open should be continuous and unbroken. This inhibits any tendency for the movement of the container to be affected by the edges of the air inlet openings. In preferred embodiments, the air inlets open into the peripheral (commonly circular) wall of the chamber, but have a depth which is less than the height of that wall so that at least part of the wall, eg the lower and/or upper part of the wall, forms an uninterrupted annular surface.
The chamber may be provided with a formation which serves to constrain the movement of the container in its orbital path. For example, a spigot or the like may be formed in the centre of the chamber. However, in practice it is commonly found that no such formation is necessary, or merely a vestigial formation, eg a small protrusion in the centre of the base of the chamber, is effective.
According to another aspect of the invention, there is provided a device having a chamber adapted to receive a container containing a unit dose of medicament in powder form, air inlet means by which air may be drawn into the chamber and mouthpiece means by which air and entrained medicament may be drawn out of the chamber., wherein the chamber is substantially circular or annular in form and is provided with one or more formations effective to constrain, in use, the container to an orbital path within the chamber.
Air preferably passes out of the chamber to the mouthpiece through a mesh or grid formed in part of the wall of the chamber. Most preferably. the mesh or grid lies in a plane which is parallel to the plane in which container moves. For example the mesh or grid may be formed in the flat base or roof of the chamber. The mesh or grid may take any suitable form provided that, in use, it serves to retain the container within the chamber whilst permitting air and entrained medicament to pass out of the chamber.
It is particularly preferred that the grid or mesh should extend over only part of the base of the chamber, most preferably the central part of the base, ie the radially outer part of the base is preferably solid. It is found that this arrangement increases the residence time of medicament dispensed from the device within the chamber and this in turn enhances the dispersion of the medicament particles. Most preferably, for a chamber with a circular of substantially circular base, the outermost part of the base forms an annulus having a width corresponding to at least 15% of the radius of the base, more preferably at least 20%.
The mouthpiece is preferably formed at the open end of a passageway or conduit which connects the chamber to the mouthpiece. A particularly compact arrangement is provided if the passageway or conduit is disposed substantially orthogonally to the axis of rotation of the container in the chamber. In other embodiments, the passageway or conduit may be oriented parallel to that axis.
The device may be manufactured from materials conventionally utilised in inhalation drug delivery devices. Examples include plastics materials such as polycarbonate, polyolefins such as polypropylene or polyethylene, and others. Other materials which may be used include metals eg aluminium stainless steel etc. Combinations of materials may be used, individual components being formed from the most suitable material in each case.
The device according to the invention may be configured for repeated use, in which case means arc provided for introducing a container into the chamber and removing the container after use. The chamber may, for example, have a removable cover, eg having a snap fit or hinged connection to the rest of the device, which can be opened to insert a container, closed during use of the device and then opened again for removal of the spent container.
In other embodiments, the device may be for single dose use. In such a case the device may be supplied with a container of medicament incorporated into the device in such a way that the dispensing aperture is sealed, the container being released from the device, and the dispensing aperture thereby opened, by the patient immediately before use.
The medicament container according to the invention may have any shape, provided that shape permits the orbital motion of the container within the chamber. However, the container is preferably circular or substantially circular, ie with the overall shape of a drum, discus or short cylinder. Such a container shape is novel and represents a further aspect of the present invention, which thus provides a unit dose of a powdered inhalation medicament contained within a cylindrical or substantially cylindrical container. The diameter of the cylinder is generally greater than its depth, most preferably about twice the depth or more.
The medicament container is most preferably cylindrical or substantially cylindrical. Most preferably, the container is formed from two cooperating components which fit together, eg with a close or snap fit. One of said components is preferably of generally cylindrical construction, and open at one end. The other component will fit closely within or about the open end of the first, thereby completing the cylindrical container. One or both of the two components may be formed with a dispensing aperture. Alternatively, the at least one dispensing aperture may be defined between the two components. Most preferably, a plurality of dispensing apertures are provided, preferably four or more, eg six or eight. The apertures may advantageously be disposed around the circumference of the cylindrical container. In other embodiments, a dispensing aperture may alternatively or in addition be provided in one or both end faces of the cylinder.
The medicament container is preferably of a material which is substantially impermeable to moisture. This is advantageous in that the need for secondary packaging is thereby reduced or eliminated. This reduces the complexity of the manufacturing operation and also simplifies use of the medicament.
Thus, according to another aspect of the present invention, there is provided a unit dose of a powdered inhalation medicament, said unit dose being contained within a container having at least one dispensing aperture, the container being of a material which is substantially impermeable to moisture.
Because the container is provided with at least one dispensing aperture it is not necessary for it to be pierced prior to use and there are therefore no problems such as those associated with the piercing of conventional gelatine capsules.
In order to prevent loss of powder from the container, the unit dose according to the invention will, prior to use, be associated with a sealing means arranged to close the at least one dispensing aperture. Thus, according to a further aspect of the invention, a medicament package containing at least one unit dose of a powdered medicament comprises a container which contains the unit dose of medicament and has at least one dispensing aperture, the container being of a material which is substantially impermeable to moisture, and a sealing means arranged to close the at least one dispensing aperture.
The medicament container may be formed from any material or combination of materials with the requisite impermeability to moisture. One preferred example is light metal sheet, eg aluminium, from which the components making up the container may be pressed and cut. Other metals include stainless steel and alloys. Other materials which may be used include plastics materials. Examples of plastics materials of low moisture permeability are high density polyethylene (eg that sold under the trade mark RIGIDEX HD6070EA), polycarbonate, polyvinylchloride, polyethylene terephthalate and polypropylene. One particular plastics material which may be suitable is the olefin-cycloolefin copolymer sold by Hoechst AG under the trade mark TOPAS.
By xe2x80x9clow moisture permeabilityxe2x80x9d is meant a permeability to water vapour which is sufficiently low that during normal storage and use of the container (and in the absence of secondary packaging such as a blister package) ingress of moisture is insufficient to affect the medicament adversely to a significant extent. Permeability may be measured by standard methods such as ASTM F1249/90. When measured by that method at a temperature of 38xc2x0 C. and 90% relative humidity the permeability of the material is preferably less than 0.5 g mm/m2 day bar, more preferably less than 0.3, and especially less than 0.1.
In general, the lower the moisture permeability of the material used for the container, the lower is the thickness of that material required to form an effective barrier to moisture. This leads to a reduction in weight and hence to a reduction in the airflow necessary to cause the container to move.
The sealing means may comprise a ring of elastomeric material which surrounds the container so as to overlie and close the at least one dispensing aperture.
Alternatively, the sealing means may be a support which carries the medicament container. For example, the sealing means may be a planar support having an opening or recess within which the container is received with a close fit such that the support overlies and closes the at least one dispensing aperture. The support may, for example, be of card or plastics material. In one embodiment, the support comprises a sheet of plastics material, the sheet having an opening dimensioned and configured closely to receive the container, and the circumference of said opening being constituted by a ring of elastomeric material. Suitable elastomeric materials include natural and synthetic rubbers, and so-called thermoplastic elastomers, eg that known as SANTOPRENE. The elastomeric material may be chemically or physically bonded or fixed to the support.
The system according to the invention may be used for the delivery of a wide range of medicaments, including any medicament which is suitable for delivery in powder form by inhalation. Inhalation will most commonly be oral inhalation, but may also be nasal inhalation, in which case the term xe2x80x9cmouthpiecexe2x80x9d will be understood to refer to a passage suitable for insertion into a nostril rather than the patient""s mouth.
Whilst the system of the invention is intended primarily for use in which inspiration by the patient leads to the necessary motion of the container and dispersion of the medicament from the container, an external source of air or other gas may alternatively be used to create the necessary airstream.
According to another aspect of the invention, there is provided a method for the administration of a powdered medicament by inhalation, which method comprises introducing into a chamber which is substantially circular or annular in form a container containing a unit dose of the medicament, the container having at least one dispensing aperture therein, and generating an airstream within the chamber so as to cause the container to follow an orbital path within the chamber.
The movement of the container within the chamber is preferably epicyclic, ie the container orbits about the centre of the chamber and also rotates about its own axis.